August 11, 2025

expert reaction to phase 1 study on a vaccine for patients with pancreatic and colorectal cancer

Phase 1 study results published in Nature Medicine looks at a vaccine for patients with pancreatic and colorectal cancer.

Dr Magnus Dillon, Clinician Scientist at The Institute of Cancer Research, London and Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust, said:

“It’s extremely promising to have a vaccine that seems to stimulate T cell activity in KRAS-driven tumours – these are generally ‘immune cold’, so therapies which stimulate immune responses in this group of patients are much needed.

“Many patients have these KRAS mutations, so an off-the-shelf vaccine could benefit lots of people – it saves the cost and time required to make a personalised vaccine.

“However, it’s a bit early to definitively tell whether this will work to prevent cancer relapse in this group of patients who have had all disease removed at surgery – larger studies will be needed.  A bigger challenge is to see if the activated immune system could also work against established tumours, which have many ways to avoid immune attack and prevent immune cells from entering.”

Prof Richard Sullivan, Director, Institute of Cancer Policy and Co-Director of the Centre for Conflict & Health Research, King’s College London, said:

“There is some interesting science in this study, but this is a long way from proving any sort of clinical utility.

“They mix colorectal cancers with pancreatic cancers – two widely different cancers with very different prognosis, even if the latter is surgically resected. The former has very good prognosis even with late stage disease whereas the latter is poor even if early stage, and resected. The arms are unbalanced with 20 pancreatic and only 5 colorectal cancers. There’s an absence of clinically measurable disease in the colorectal cancers and is not the same as pancreatic cancers. This really does not help one bit in understanding efficacy of the results here.

“Results are also confounded by using additional immuno oncology. And if you look at one (mixed) overall survival (OS) curve – by 18 months half the patients have died, and only 2 by 24 months still alive – and they are (as expected) the bowel cancer patients who’d relapsed. I can’t see any dramatic efficacy signals in this data, at all.

“All this paper really says is that the vaccine generates polyfunctional CD4+ and CD8+ T cell immunity to mKRAS. We’ve been here before with this sort of approach and not have it translate into tangible efficacy.”

Dr Khurum Khan, Consultant Medical Onocologist, University College London Hospitals NHS Foundation Trust, said:

Does the press release accurately reflect the science?

“Pancreatic ductal adenocarcinoma (PDAC) and metastatic colorectal cancer (mCRC) are highly driven by KRAS signaling, with mutations present in approximately 95% of PDAC and 50% of mCRC cases. Minimal residual disease (MRD) has emerged as an important biomarker to stratify relapse risk, and recent studies have validated its role in identifying patients at high risk of progression. 

“This study evaluated patients with MRD following standard treatment and assessed the ELI-002 2P vaccine, an off-the-shelf immunotherapy designed to target mutant KRAS proteins. While phase 1 trials are inherently designed to evaluate safety and immunogenicity, the immune and clinical signals observed here are encouraging. The press relase correctly identifies that this is a phase 1 trial in pancreatic and colorectal cancer. It accurately reports that 68% of patients had strong T cell responses and that this correlated with longer recurrence-free and overall survival. It also Notes that the vaccine may promote antigen spreading, which was shown in the study.

“That said, it’s important to recognize that the data, while promising, do not yet establish efficacy, and we cannot assume these findings will translate to benefit in larger phase 2 or phase 3 trials. The press release is directionally accurate but leans toward optimism in suggesting clinical benefit. Nonetheless, this is a very exciting area of research that not only reinforces the clinical utility of MRD as a selection tool but also highlights the potential for immunologic intervention in early disease. I would be cautious with the phrase ,”helps to prolong long-term recurrence-free survival” implies efficacy, whereas the trial only establishes correlation (not causality). The risk is that this phrase effectively oversimplifies a complex immuniogenic approach in a relatively small cohort of patients. Moreoever, saying that it “exceeds historical control data” is suggestive of comparative efficacy, but no control arm was used in this study.

Is this good quality research? Are the conclusions backed up by solid data?

“The scientific data presented are robust, and the fact that this study is published in Nature Medicine ,which is one of the most reputable journals in the field further supports the quality and novelty of the work.

“This is a well-conducted and thoughtfully designed early-phase trial, which employs advanced immunologic assays to characterize KRAS-specific T cell responses and correlate them with clinical outcomes, including relapse-free survival (RFS) and overall survival (OS). The observed association between strong mKRAS-specific immune responses and improved outcomes is supported by statistically significant hazard ratios and tumor biomarker clearance, adding biological and clinical plausibility to the findings.

“That said, it’s important to acknowledge that this is still a phase 1 trial, involving a small number of patients (n = 25)and not powered for efficacy conclusions. Therefore, while the results are promising and hypothesis-generating, they remain preliminary and will need to be validated in larger, randomized studies before clinical benefit can be confirmed.

How does this work fit with the existing evidence?

“This study builds on a solid foundation of prior research demonstrating that KRAS mutations are central oncogenic drivers in a range of malignancies, most notably pancreatic cancer (PDAC) and colorectal cancer (CRC), but also in lung cancer and others. While KRAS is not formally considered a “tumor-agnostic” target in the regulatory sense, its presence across multiple cancer types makes it a highly relevant and attractive target for broad-spectrum therapeutic strategies. The success of this vaccine approach could therefore have broader implications beyond PDAC and mCRC.

“Secondly, the concept of minimal residual disease (MRD) as a predictor of relapse is already well-established in solid tumors, including PDAC and CRC. What this study does uniquely is advance the management of MRD beyond traditional cytotoxic chemotherapy, by leveraging immune-mediated targeting of persistent cancer-associated mutations. Specifically, ELI-002 2P targets mutant KRAS antigens in the MRD setting, offering a potentially less toxic and more precise way to eliminate residual disease a significant step forward in MRD-directed therapy.

“Finally, this study also contributes to the growing field of cancer vaccines, which have long been investigated but have often failed due to inadequate immune activation or poor delivery to lymphoid tissue. Here, the use of an amphiphile-conjugated vaccine platform appears to improve lymph node targeting and T cell priming, resulting in durable and functionally relevant immune responses. The observation of antigen spreading further suggests that this approach may help broaden the immune response beyond the initial targets, which could be critical for long-term control and prevention of relapse.

“Taken together, this study fits well with existing evidence on KRAS biology, builds on MRD as a clinical concept, and meaningfully contributes to the evolving field of cancer immunoprevention and vaccine-based therapy.

Have the authors accounted for confounders? Are there important limitations to be aware of?

“The authors have made a commendable effort to account for key immunological and clinical variables. Notably, they stratified patients based on the strength of mKRAS-specific T cell responses and correlated this with outcomes such as radiographic relapse-free survival (RFS) and overall survival (OS). They also acknowledged the potential impact of subsequent therapies, such as chemotherapy or immune checkpoint inhibitors, and censored RFS data appropriately in those cases. This suggests an awareness of clinical confounders and an effort to present the data responsibly.

“The lack of a control group is a recognised limitation, but it is also a natural and expected constraint in phase 1 trials, which are designed primarily to assess safety, dosing, and biological activity rather than definitive clinical efficacy. It would be inappropriate to view this as an oversight, as randomised comparisons are better suited for later-phase trials.

“There are, however, some additional variables that could influence outcomes and were not the focus of this study. For instance, baseline tumor burden, underlying immune fitness, and tumour microenvironment characteristics may all play roles in shaping immune responses and clinical benefit. While these factors were not deeply explored here, that is understandable given the trial’s early-phase nature and specific focus on vaccine-induced T cell responses.

“In summary, within the scope and goals of a phase 1 study, the authors have appropriately addressed key confounders and transparently reported the limitations. Future studies, particularly randomised, controlled trials will be better positioned to evaluate the contribution of these other variables and to isolate the true therapeutic impact of the vaccine.

What are the implications in the real world? Is there any overspeculation?

“This study presents promising scientific and clinical potential, particularly if the findings are validated in larger, statistically powered trials. The ability of the ELI-002 2P vaccine to elicit strong mKRAS-specific T cell responses and the correlation of those responses with improved relapse-free and overall survival  is compelling and biologically plausible. If these early signals are replicated, such an approach could significantly shift how we manage patients with minimal residual disease (MRD), particularly in pancreatic and colorectal cancer, where effective options remain limited.

“That said, it is important to recognize that any implications of durable protection or survival benefit remain speculative at this stage. This was a non-randomized, small-scale phase 1 study, designed to assess safety and immunogenicity, not efficacy. No definitive conclusions can be drawn about the vaccine’s comparative effectiveness versus standard-of-care therapies, such as adjuvant chemotherapy, which remains the current standard for MRD-positive patients.

“As future randomised controlled trials are conducted, it will be critical to determine whether the vaccine offers not only biological activity, but also clinical superiority or equivalence to existing approaches. This includes evaluating not just efficacy, but also cost-effectiveness, especially in the current healthcare environment where sustainability and access are increasingly important considerations.

“Nonetheless, the enthusiasm in the field is not unwarranted. Recent data from the DYNAMIC-2 trial in colorectal cancer has shown that chemotherapy is often ineffective at preventing relapse in MRD-positive patients. This highlights the urgent need for novel, biology-driven interventions, and positions ELI-002 2P as a rational and potentially transformative strategy. The concept of using a vaccine to both clear MRD and prime the immune system against relapse represents a paradigm shift, albeit one that still requires rigorous testing.”

‘Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results’ by Zev A. Wainberg et al. was published in Nature Medicine at 16:00 UK time on Monday 11^th August. 

DOI: https://doi.org/10.1038/s41591-025-03876-4

Declared interests

Dr Magnus Dillon: None

Prof Richard Sullivan: None

Dr Khurum Khan: No interests to declare